8-Amino-5,6,7,8-tetrahydroquinoline in iridium(iii) biotinylated Cp* complex as artificial imine reductase

Diamine ligands I-IV coordinated to an iridium metal complex with the biotin moiety anchored to the Cp* ring were investigated. This strategy, in contrast to the traditional biotin-streptavidin technology that uses a biotinylated ligand in the artificial imine reductase, is practical for envisaging how the enantiodiscrimination by different Streptavidin (Sav) mutants could influence the chiral environment of the metal cofactor. Only in the case of (R)-CAMPY IV did the chirality at the metal centre and the second coordination sphere environment, which was dictated by the host protein, operate in a synergistic way, producing better enantioselectivity at a S112M Sav catalyst/catalyst ratio of 1.0 : 2.5. Under these optimized conditions, the artificial imine reductase afforded a good enantiomeric excess (83%) in the asymmetric transfer hydrogenation of 6,7-dimethoxy-1-methyl-3,4-dihydroisoquinoline

Novel platinum agents and mesenchymal stromal cells for thoracic malignancies : state of the art and future perspectives

Introduction: Non-small cell lung cancer and malignant pleural mesothelioma represent two of the most intriguing and scrutinized thoracic malignancies, presenting interesting perspectives of experimental development and clinical applications. Areas covered: In advanced non-small cell lung cancer, molecular targeted therapy is the standard firstline treatment for patients with identified driver mutations; on the other hand, chemotherapy is the standard treatment for patients without EGFR mutations or ALK rearrangement or those with unknown mutation status. Once considered an ineffective therapy in pulmonary neoplasms, immunotherapy has been now established as one of the most promising therapeutic options. Mesenchymal stromal cells are able to migrate specifically toward solid neoplasms and their metastatic localizations when injected intravenously. This peculiar cancer tropism has opened up an emerging field to use them as vectors to deliver antineoplastic drugs for targeted therapies. Expert opinion: Molecular targeted therapy and immunotherapy are the new alternatives to standard chemotherapy. Mesenchymal stromal cells are a new promising tool in oncology and\u2014although not yet utilized in the clinical practice, we think they will represent another main tool for cancer therapy and will probably play a leading role in the field of nanovectors and molecular medicine

Asymmetric Hydrogenation vs Transfer Hydrogenation in the Reduction of Cyclic Imines

A comparison between the two most common reduction approaches for obtaining chiral amines, asymmetric hydrogenation (AH) versus asymmetric transfer hydrogenation (ATH), was accomplished by using iridium complexes based on atropoisomeric diphosphines and cyclic diamines as ligands respectively. Seven substrates, different in electronic and steric properties, were screened applying both reduction methods. For AH the best results in terms of enantioselectivity (e.e. up to 64%) were obtained by using [Ir(COD)(TetraMe-BITIOP)]Cl in the presence of DCDMH as additive. ATH was carried out with [IrCp*(CAMPY)Cl]Cl as catalyst, allowing the obtainment of the products with appreciable e.e. (up to 76%)

Efficient methodology to produce a duloxetine precursor using whole cells of Rhodotorula rubra

Different types of yeasts were employed as biocatalysts in the reduction of \u3b2-ketonitriles. The red microorganism, Rhodotorula rubra, was selected as the best performing catalyst in the reduction of different substituted ketonitriles giving total stereoselectivity in most cases (90-99% ee). In particular, its use as fresh and lyophilised cells was expanded to a semi-preparative scale for the production of the duloxetine precursor 1a. R. rubra was screened in the reduction of alkylation products in comparison with Pichia henricii for assignment of configuration of products 2a and 11a after derivatisation with S-MPA

Exploiting coordination geometry to selectively predict the r-donor and p-acceptor abilities of ligands: a back-and-forth journey between electronic properties and spectroscopy

Coordination geometry switches the carbonyl stretching frequency into a selective probe of the σ-donor and π-acceptor abilities of ligands

Asymmetric Hydrogenation of 1-aryl substituted-3,4-Dihydroisoquinolines with Iridium Catalysts Bearing Different Phosphorus-Based Ligands

Starting from the chiral 5,6,7,8-tetrahydroquinolin-8-ol core, a series of amino-phosphorusbased ligands was realized. The so-obtained amino-phosphine ligand (L1), amino-phosphinite (L2) and amino-phosphite (L3) were evaluated in iridium complexes together with the heterobiaryl diphosphines tetraMe-BITIOP (L4), Diophep (L5) and L6 and L7 ligands, characterized by mixed chirality. Their catalytic performance in the asymmetric hydrogenation (AH) of the model substrate 6,7-dimethoxy-1-phenyl-3,4-dihydroisoquinoline 1a led us to identify Ir-L4 and Ir-L5 catalysts as the most eective. The application of these catalytic systems to a library of dierently substituted 1-aryl-3,4-dihydroisoquinolines aorded the corresponding products with variable enantioselective levels. The 4-nitrophenyl derivative 3b was obtained in a complete conversion and with an excellent 94% e.e. using Ir-L4, and a good 76% e.e. was achieved in the reduction of 2-nitrophenyl derivative 6a using Ir-L5

Antiproliferative effects of chalcones on T cell acute lymphoblastic leukemia‐derived cells: Role of PKCβ

In this study, a series of 20 chalcone derivatives was synthesized, and their antiproliferative activity was tested against the human T cell acute lymphoblastic leukemia\u2010derived cell line, CCRF\u2010CEM. On the basis of the structural features of the most active compounds, a new library of chalcone derivatives, according to the structure\u2013activity relationship design, was synthesized, and their antiproliferative activity was tested against the same cancer cell line. Furthermore, four of these derivatives (compounds 3, 4, 8, 28), based on lower IC50 values (between 6.1 and 8.9 \u3bcM), were selected for further investigation regarding the modulation of the protein expression of RACK1 (receptor for activated C kinase), protein kinase C (PKC)\u3b1 and PKC\u3b2, and their action on the cell cycle level. The cell cycle analysis indicated a block in the G0/G1 phase for all four compounds, with a statistically significant decrease in the percentage of cells in the S phase, with no indication of apoptosis (sub\u2010G0/G1 phase). Compounds 4 and 8 showed a statistically significant reduction in the expression of PKC\u3b1 and an increase in PKC\u3b2, which together with the demonstration of an antiproliferative role of PKC\u3b2, as assessed by treating cells with a selective PKC\u3b2 activator, indicated that the observed antiproliferative effect is likely to be mediated through PKC\u3b2 induction

Vancomycin-Iridium (III) Interaction: An Unexplored Route for Enantioselective Imine Reduction

The chiral structure of antibiotic vancomycin (Van) was exploited as an innovative coordination sphere for the preparation of an IrCp* based hybrid catalysts. We found that Van is able to coordinate iridium (Ir(III)) and the complexation was demonstrated by several analytical techniques such as MALDI-TOF, UV, Circular dichroism (CD), Raman IR, and NMR. The hybrid system so obtained was employed in the Asymmetric Transfer Hydrogenation (ATH) of cyclic imines allowing to obtain a valuable 61% e.e. (R) in the asymmetric reduction of quinaldine 2. The catalytic system exhibited a saturation kinetics with a calculated eciency of Kcat/KM = 0.688 h1mM

Novel 3,3-disubstituted oxindole derivatives. Synthesis and evaluation of the anti-proliferative activity

3,3-Disubstituted oxindole derivatives bearing a nitrogen atom at the C-3 position have been synthesized starting from 3-alkyl oxindole through a metal free pathway. These derivatives have been tested in five human tumor cell lines (PC3, MCF7, SW620, MiaPaca2 and A375) and on primary cells (PBMCs) from healthy donors providing compound 6d showing a strong anticancer effect in all cancer lines on the low micromolar range

“In situ” Activation of Racemic RuII Complexes: Separation of trans and cis Species and Their Application in Asymmetric Reduction

Ruthenium(II) dichlorides with racemic atropos-biaryl-based diphosphanes and optically active 1,2-diphenylethane-1,2-diamine (DPEN) as ligands have been synthesised. trans and cis isomers were formed due to the low basicity of the diphosphane ligands, in particular, with BITIANP and BIMIP. The trans and cis species were easily separated by filtration. In particular, when rac-BITIANP was used in combination with chiral DPEN, the asymmetric separation of optically pure complexes in cis and trans arrangements was realised and they were used as precatalysts in the asymmetric hydrogenation of ketones. Matching and mismatching combinations exhibited different performances